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NDRG2 Is Involved in the Oncogenic Properties of Renal Cell Carcinoma and Its Loss Is a Novel Independent Poor Prognostic Factor After Nephrectomy

  • Translational Research and Biomarkers
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Abstract

Background

Although NDRG2 is a candidate tumor suppressor, its exact role in renal cell carcinoma (RCC) is not fully understood. We investigated the functional role of NDRG2 and its clinical relevance in RCC tumorigenesis.

Methods

NDRG2 expression and its clinical implications in clear cell RCC were evaluated. Biological function was assessed by a proliferation assay, anchorage-independent growth assay, and wound healing and transwell migration assays in RCC cell lines overexpressing NDRG2 coupled with an investigation of the effects of NDRG2 expression on the epithelial–mesenchymal transition (EMT).

Results

NDRG2 was differentially expressed in patients with RCC. A loss of NDRG2 was significantly associated with a higher proportion of tumors >10 cm and a high nuclear grade. Furthermore, multivariate analyses indicated that a loss of NDRG2 was an independent poor prognostic factor for patient survival (recurrence-free survival, hazard ratio 7.901; disease-specific survival, hazard ratio 15.395; overall survival, hazard ratio 11.339; P < 0.001 for all parameters). NDRG2 expression inhibited the anchorage-independent growth and migration of RCC cells. NDRG2 expression also modulated the expression of EMT-related genes such as Snail, Slug, and SIP1, and it decreased EMT signaling in RCC cells. Finally, NDRG2 recovered E-cadherin expression in E-cadherin-negative RCC cells.

Conclusions

These results indicate that a lack of NDRG2 is associated with oncogenic properties through the loss of its role as a tumor suppressor, and that NDRG2 is an independent poor prognostic factor predicting survival in clear cell RCC, suggesting that it can serve as a novel prognostic biomarker.

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Acknowledgment

This work was supported by a grant of the Research Center for Women’s Diseases through the National Research Foundation of Korea (NRF) (R11-2011-0001386), and the NRF grants funded by the Ministry of Education, Science and Technology of Korea (MEST) (No. 2011-0006229).

Conflict of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Pathology, Cancer Research Institute, and Infection Signaling Network Research Center, Chungnam National University School of Medicine, Daejeon, Republic of Korea

    Zhe Long Liang MD, Song Mei Huang MD & Jin Man Kim MD

  2. Department of Biological Science and the Research Center for Women’s Disease, Sookmyung Women’s University, Seoul, Republic of Korea

    Kyeongah Kang PhD, Sukjoon Yoon PhD & Jong-Seok Lim PhD

  3. Department of Urology and Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea

    Jae Sung Lim MD

  4. Department of Internal Medicine and Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea

    Hyo Jin Lee MD

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  1. Zhe Long Liang MD
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  2. Kyeongah Kang PhD
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  3. Sukjoon Yoon PhD
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  4. Song Mei Huang MD
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  5. Jae Sung Lim MD
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Correspondence to Jong-Seok Lim PhD or Hyo Jin Lee MD.

Additional information

Zhe Long Liang and Kyeongah Kang contributed equally to this work.

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Liang, Z.L., Kang, K., Yoon, S. et al. NDRG2 Is Involved in the Oncogenic Properties of Renal Cell Carcinoma and Its Loss Is a Novel Independent Poor Prognostic Factor After Nephrectomy. Ann Surg Oncol 19, 2763–2772 (2012). https://doi.org/10.1245/s10434-011-2204-3

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